Deputy coach Patrick Collot will take over on an interim basis.
The 55-year-old Corsican has agreed terms to leave "in a friendly manner," a statement from the northern outfit said.
Antonetti paid the price for a disastrous start to the season with the 2011 Ligue 1 winners sitting second from bottom of the table with nine losses from 13 games.
Antonetti took over a year ago in place of Herve Renard and after initially struggling finished the season superbly, finishing fifth in the league and runners-up to Paris Saint-Germain in the League Cup final.
Deputy coach Patrick Collot, a 49-year-old former player with the club, will take over on an interim basis.